Compounds of the formula ##STR6## where T is the theophyllinyl-(7)-residue, Alk is a straight or branched alkylene chain having 2 to 4 carbon atoms and R is hydrogen or a C.sub.1 -C.sub.6 alkyl group, n is the number 1 or 2 and the phenolic OH groups and/or the basic nitrogen atom can be protected are important intermediate products for the production of pharmacolgically useful compounds of the formula ##STR7##
To produce such intermediate products of formula A it is recommended in German Pat. No. 1 545 725 to react the benzylaminoalkyl theophyllines of formula II with the halogeno ketones of formula IIIa ##STR8##
In this reaction it is frequently suitable, especially in the case where n is 2 to protect the OH groups through acyl or benzyl groups. Examples of this are described in German Offenlegungsschrift No. 2 136 643 (and related Klingler U.S. Pat. No. 3,728,346) as well as in Klingler, Arzneimettelforschung, Volume 27, pages 4-14 (1977). Thus, for example, the process given on page 13 under 4.7.1 to 4.7.3 of this publication serves to produce 7-{3-[2-(3,5-dihydroxyphenyl)-2-oxo-ethyl-benzylaminol]- propyl}-theophylline with advantage compared to the process described in Example 2 of German Offenlegungsschrift No. 1 545 725 with unprotected phenolic hydroxy groups.
The oxygen sensitivity of intermediate products of formula IIIa can be eliminated by the acetyl protective group. Besides for example the 3,5-diacetoxy-.alpha.-bromacetophenone is easily available by bromination of the commercial 3,5-diacetoxyacetophenone, while the 3,5-dihydroxy-.alpha.- chloracetophenone used in Example 2 of German Offenlegungsschrift No. 1 545 725 must be constructed in a four-step synthesis from 3,5-dihydroxybenzoic acid (see for the 2,5- isomer Koetzel, J. Org. Chem., Volume 20, pages 38-49 (1955)).
Based on the described advantages, for example, the process starting from 3,5-diacetoxyacetophenone is suited as the starting place for a commercial process of production. However, in practice upon enlargement of the amounts of the ingredients, especially on a commercial scale, there occur the following important difficulties:
1. The bromoketone obtained by bromination of the dialkanoyloxyacetophenone always contains large amounts (for example 10-20%) of more highly brominated by-products (di and tribromoketones as well as nucleus brominated products). These by-products cannot be removed in satisfactory manner.
2. The yields in the condensation of the bromoketone III obtained in impure form by the customary bromination with the amine of formula II are particularly unsatisfactory with large scale additions.
3. The thus obtained intermediate product IV in the deacylation produces a too impure product for the subsequent hydrogenation. The recrystallization required therefor is much too full of loss on a commercial scale of production.